Interesting find about creatine

[Sammich]

I was just browsing medical studies for info about creatine and hypertension (since my BP is up since I've been eating all the creatine in the world), and I stumbled across this:

The Effect of L-Arginine and Creatine on Vascular Function and Homocysteine Metabolism

Background
Studies with L-arginine supplementation have shown inconsistent effects on endothelial function. The generation of guanidinoacetate (GAA) from L-arginine with subsequent formation of creatine and homocysteine and consumption of methionine may reduce the pool of L-arginine available for nitric oxide generation. Experimental studies suggest that creatine supplementation might block this pathway. We sought to determine the effects of L-arginine, creatine, or the combination on endothelium-dependent vasodilation and homocysteine metabolism in patients with coronary artery disease.

Methods
Patients with coronary artery disease were randomized to L-arginine (9gm/day), creatine (21gm/day), L-arginine plus creatine, or placebo for 4 days (n=26–29/group). Brachial artery flow-mediated dilation and plasma levels of L-arginine, creatine, homocysteine, methionine, and GAA were measured at baseline and follow up.

Results
L-arginine and creatine supplementation had no effects on vascular function. L-arginine alone increased GAA (P<0.01) and the ratio of homocysteine to methionine (P<0.01) suggesting increased methylation demand. The combination of creatinine and L-arginine did not suppress GAA production or prevent the increase in homocysteine-to-methionine ratio. Unexpectedly, creatine supplementation (alone or in combination with L-arginine) was associated with an 11 to 20% increase in homocysteine concentration (P<0.05), which was not attributable to worsened renal function, providing evidence against an effect of creatine on decreasing methylation demand.

Conclusion
The present study provides no evidence that L-arginine supplementation improves endothelial function and suggests that L-arginine may increase methylation demand. Creatine supplementation failed to alter the actions of L-arginine on vascular function or suppress methylation demand. The unexpected increase in homocysteine levels following creatine supplementation could have adverse effects and merits further study, since creatine is a commonly used dietary supplement.

Their study suggests creatine supplementation might raise homocysteine levels. High levels of homocysteine are strongly associated with cardiovascular disease and has other very nasty effects as well. I thought this was noteworthy enough to post.

[bbjeff86]

Very Interesting. Thanks for posting. One study doesn't prove anything, but it's good to bring to peoples attention so they can look into it further, and take their health into account when trying to increase size/strength.

It would be interesting to see a similar study done on those who don't already have CAD.

[Sammich]

Very Interesting. Thanks for posting. One study doesn't prove anything, but it's good to bring to peoples attention so they can look into it further, and take their health into account when trying to increase size/strength.

It would be interesting to see a similar study done on those who don't already have CAD.

Right. This doesn't prove anything, but it's a good place to start thinking.

[mentalflex]

OK, because I love my creatine I want to dig a little deeper and find some additional studies on creatine and cardiovascular health. Here are a few articles/studies that i came across.

Study 1: Effect of creatine supplementation as a potential adjuvant therapy to exercise training in cardiac patients: a randomized controlled trial

Abstract

Objective: To investigate the effect of oral creatine supplementation in conjunction with an exercise programme on physical fitness in patients with coronary artery disease or chronic heart failure.

Design: Single centre double-blind randomized placebo controlled trial.

Setting: Cardiac rehabilitation centre.

Subjects and intervention: 70 (4 women) cardiac patients (age 57.5 (8.4) years) were randomized to a placebo (n = 37) or creatine (n = 33) treatment for three months. Combined aerobic endurance and resistance training (three sessions/ week) was performed during supplementation.

Main Measures: Aerobic power was determined during graded bicycle testing, knee extensor peak isometric and isokinetic strength, endurance and recovery were assessed by an isokinetic dynamometer, and health related quality of life was evaluated with the SF-36 and MacNew Heart Disease questionnaires. In addition, blood samples were taken after an overnight fast and 24 hour urinary collection was performed.

Results: At baseline there were no significant differences between both groups. We observed main time effects for aerobic power, muscle performance, health related quality of life, high density lipoprotein cholesterol and triglycerides (pre vs post; P<0.05 for all). However, changes after training were similar between placebo group and creatine group (P>0.05). Further, no detrimental effect on renal or liver function was observed nor were there any reports of side effects.

Conclusion: Oral creatine supplementation in combination with exercise training does not exert any additional effect on the improvement in physical performance, health related quality of life, lipid profile in patients with coronary artery disease or chronic heart failure than exercise training alone.

http://cre.sagepub.com/content/24/11/988.abstract

Study 2: Effects of creatine supplementation on aerobic power and cardiovascular structure and function

This project aimed to determine 1) whether creatine (Cr) supplementation affects cardiovascular structure and function and 2) to examine its effect on aerobic power. Eighteen males undertook aerobic testing on a cycle ergometer and echocardiographic assessment of the heart. The experimental group (N=9) ingested 20g·day−1 of Cr for seven days followed by 10g·day−1 for a further 21 days. The control group (N=9) followed an identical protocol ingesting a placebo for the same period. Assessment was performed pre-, mid- (seven days) and post-testing (28 days). A MANOVA with repeated measures was used to test for group differences before and after supplementation. The Cr group demonstrated a significant increase in body mass for the pre-mid (1.0±0.6 kg) and the pre-post (1.5±0.7 kg) testing occasions. Submaximal V̇O2 decreased significantly from the pre-mid and pre-post testing occasions by between 4.8% to 11.4% with Cr supplementation at workloads of 75 W and 150 W. Other oxygen consumption, measures and exercise time to exhaustion, for the Cr group, showed decreasing trends that approached significance. Additionally, there was a significant pre-post decrease in maximum heart rate of 3.7%. There were no changes in any of the echocardiographic or blood pressure measures for either group. The present results suggest short term Cr supplementation has no detectable negative effect on cardiac structure or function. Additionally, Cr ingestion improves submaximal cycling efficiency. These results suggest that the increase in efficiency may be related to peripheral factors such an increase in muscle phosphocreatine, rather than central changes.

http://www.sciencedirect.com/science/article/pii/S1440244005800416

Study/Research Review: Safety of Creatine Supplementation

Adam M. Persky and Eric S. Rawson


Abstract
The literature on creatine supplementation supporting its efficacy has grown rapidly and has included studies in both healthy volunteers and patient populations. However, the first rule in the development of therapeutic agents is safety. Creatine is well-tolerated in most individuals in short-term studies. However, isolated reports suggest creatine may be associated with various side effects affecting several organ systems including skeletal muscle, the kidney and the gastrointestinal tract. The majority of clinical studies fail to find an increased incidence of side effects with creatine supplementation. To date, studies have not found clinically significant deviations from normal values in renal, hepatic, cardiac or muscle function. Few data are available on the long-term consequences of creatine supplementation

http://www.springerlink.com/content/lq031gu7ur57n745/

Study: Oral Creatine Supplements Lower Plasma Homocysteine Concentrations in Humans

Clin Lab Sci 2004;17(2):102

Abstract:
OBJECTIVE: To determine if oral creatine supplements will
lower the concentration of total plasma homocysteine (tHcy).

SETTING/PARTICIPANTS: Apparently healthy volunteers,
at least 19 years old, were recruited from the University
of South Alabama and surrounding community.

DESIGN/INTERVENTION/MAIN OUTCOME:
Participants took multi-vitamins daily for four weeks, then
were randomly divided into two groups. The control group
(C) continued to take multi-vitamins daily for an additional
four weeks. The experimental group (EX) took multivitamins
plus an amount of creatine each day equal to twice
their daily creatinine excretion, for the additional four weeks.
Total plasma homocysteine concentrations were measured
in all participants at the beginning and at the end of the
second four week interval.

RESULTS: There were no statistically significant differences
between the two groups in age, initial tHcy, serum folate,
erythrocyte folate, serum vitamin B12, or creatinine excretion.
After four weeks of creatine supplements, tHcy in EX
changed by an average of –0.9 μmol/L (range: -1.8 to 0.0),
compared to an average change of +0.2 μmol/L in C (range:
–0.6 to 0.9) during the same four weeks. The difference in
the changes in tHcy between the two groups was statistically
significant (p <0.01).

CONCLUSION: Creatine supplements may be an effective
adjunct to vitamin supplements for lowering tHcy.

ABBREVIATIONS: C = group of participants taking only
multivitamins; EX = group of participants taking multivitamins
plus creatine; Hcy = homocysteine; SAH = Sadenosylhomocysteine;
SAM = S-adenosylmethionine; tHcy

**Interesting thing about this is that the findings are the exact opposite of Sammich's article**
= concentration of total plasma homocysteine.


I came across a lot of articles stating that creatine supplementation may actually be beneficial in improving cardiovascular functioning, particularly in individuals with congestive heart failure. There definitely needs to be more research on this subject...

[Sammich]

I fucking hate science.

[homonunculus]

There's an external validity issue here, Sammichy, too (which I hope drops you down to a Defcon 2 or below):

From the Discussion:

"The subjects in our study were selected due to the presence of coronary artery disease; however, many of the subjects also had chronic kidney disease. This is evident by a mean glomerular filtration rate of 68.7 ± 27.7 mL/min (by the Cockcroft-Gault formula) -consistent with stage 2 disease by the National Kidney Foundation-Dialysis Outcomes Quality Initiative Clinical
Practice Guidelines.43"

---------

-S

[Sammich]

I still hate science.

[mentalflex]

There's an external validity issue here, Sammichy, too (which I hope drops you down to a Defcon 2 or below):

Knew I'd get called out on one of those studies. A certain degree of research bias may have been in play on my part. Creatine has served many of us all too well to think it would do us harm.

[KT-John]

Sammich

Thanks for posting that. Interestingly, however, I was under the impression that creatine supplementation actually lowered homocysteine due to the fact that 70% (reportedly) of homocysteine is produced by the body's own manufacturing of creatine. If this is true, then it would make sense that creatine supplementation would negate the body's need to manufacture creatine, thus lowering homocysteine levels. Perhaps this is not the case as the study you presented shows.

----------------------

How creatine lengthens your lifespan
Animal studies show that creatine [structural formula below] works as a life extender. Nutritionists at the University of Sao Paulo did experiments with rats and may have discovered why. The power sports supplement reduces the production of the risky amino acid homocysteine and protects cells against damage.

Creatine is a molecular battery. Cells stick energy-providing phosphate groups on to creatine molecules, and pull them off again when they need them. That’s why power athletes can manage longer sets if they take creatine. The human body gets creatine from foods such as fish and meat, but also makes the substance itself from the amino acids arginine and glycine. When producing creatine, the body also uses methyl groups from the S-adenosylmethionine molecule, which as a result change into homocysteine. Seventy percent of the homocysteine in your body is produced as a result of your body manufacturing creatine.

People with high amounts of homocysteine in their blood are not healthy and have an increased chance of a heart attack. How this happens is not known. Until recently researchers thought that homocysteine itself was responsible for this, but this theory has been rejected. [That extremely high concentrations of homocysteine, such as are found in metabolic disorders or serious doping use, do pose considerable risk is not disputed by researchers – ed.] In trials, vitamin B supplements did lower the concentration of homocysteine, but did not reduce the risk of a heart attack. Apparently something goes wrong in the body’s homocysteine production process.

And that’s where creatine comes into the equation. Put creatine into a body, and the production of homocysteine goes down.

The Brazilians were able to confirm this. They gave rats feed consisting of 2 percent creatine [DCr] for a period of four weeks. Another group were first given 5 g creatine per kg bodyweight for 5 days, and after that feed consisting of 2 percent creatine. A control group got no creatine at all.



The creatine supplement reduced the concentration in the blood of TBARS, a marker for free radical damage. The more creatine the rats had in their blood, the lower the TBARS concentration. The concentration of free radicals, such as hydrogen peroxide, was also lower.

What’s more, the lower the TBARS concentration in the rats’ blood, the lower their homocysteine level.

Creatine also reduced the production of the endogenous antioxidant glutathione. Glutathione is a tripeptide that is used by detoxifying enzymes like glutathione S-transferase. The researchers suspect that creatine supplementation results in the body needing less glutathione. They think that creatine itself works as an antioxidant.
Research on creatine and homocysteine is doubly interesting for power athletes. Because they have more muscle mass, their body makes more creatine and they have more homocysteine in their body. That’s why the homocysteine level goes down in transsexuals that change from man to woman, and thus give up muscle mass. [Atherosclerosis. 2003 May;168(1):139-46.] Using steroids raises the concentration of homocysteine even further. In studies on chemical bodybuilders, a raised homocysteine level heralded a fatal heart attack. [British Journal of Sports Medicine 2006;40:644-8.]

Source:
Br J Nutr. 2009 Jul;102(1)110-6.

[KT-John]

The above article was found at: http://ergo-log.com/creatinelongevity2.html

[Rocky]

i just recently reconsidered my opinion on creatine. I stgated using it a few months back just as an experiment and just over a week ago i stopped using it and my strength has diminished some (average of 2 reps less on heavy compound movements)...everything else was kept the same as far as diet and training,so that means that creatine did help me get stronger

[bbjeff86]

i just recently reconsidered my opinion on creatine. I stgated using it a few months back just as an experiment and just over a week ago i stopped using it and my strength has diminished some (average of 2 reps less on heavy compound movements)...everything else was kept the same as far as diet and training,so that means that creatine did help me get stronger

Nobody is debating that it helps you get stronger.... I think it's probably the one supplement that pretty much everyone can agree works...

What is being discussed here are what could potentially be some health risks in the long term...

[Rocky]

Nobody is debating that it helps you get stronger.... I think it's probably the one supplement that pretty much everyone can agree works...

What is being discussed here are what could potentially be some health risks in the long term...

bodybuilders are known to eat,drink,pop,and inject whatever will get them to their goal yet a study on possible long-term effects of creatine gets us all in a frenzy? How ironic.

[Ken "Skip" Hill]

bodybuilders are known to eat,drink,pop,and inject whatever will get them to their goal yet a study on possible long-term effects of creatine gets us all in a frenzy? How ironic.

Not all of us are known for that. I agree that as a group, bodybuilders tend to have a "whatever it takes" mentality but not all of us are willing to do that.

Skip

[bluey]

^^ like ^^